The Significance of α-Synuclein, Amyloid-β and Tau Pathologies in Parkinson's Disease Progression and Related Dementia
- 11 September 2013
- journal article
- Published by S. Karger AG in Neurodegenerative Diseases
- Vol. 13 (2-3), 154-156
- https://doi.org/10.1159/000354670
Abstract
Background: Dementia is one of the milestones of advanced Parkinson's disease (PD), with its neuropathological substrate still being a matter of debate, particularly regarding its potential mechanistic implications. Objective: The aim of this study was to review the relative importance of Lewy-related α-synuclein and Alzheimer's tau and amyloid-β (Aβ) pathologies in disease progression and dementia in PD. Methods: We reviewed studies conducted at the Queen Square Brain Bank, Institute of Neurology, University College London, using large PD cohorts. Results: Cortical Lewy- and Alzheimer-type pathologies are associated with milestones of poorer prognosis and with non-tremor predominance, which have been, in turn, linked to dementia. The combination of these pathologies is the most robust neuropathological substrate of PD-related dementia, with cortical Aβ burden determining a faster progression to dementia. Conclusion: The shared relevance of these pathologies in PD progression and dementia is in line with experimental data suggesting synergism between α-synuclein, tau and Aβ and with studies testing these proteins as disease biomarkers, hence favouring the eventual testing of therapeutic strategies targeting these proteins in PD.Keywords
This publication has 28 references indexed in Scilit:
- Distinct α-Synuclein Strains Differentially Promote Tau Inclusions in NeuronsCell, 2013
- Pathologic Accumulation of α-Synuclein and Aβ in Parkinson Disease Patients With DementiaArchives of Neurology, 2012
- Grey matter volume correlates of cerebrospinal markers of Alzheimer-pathology in Parkinson's disease and related dementiaParkinsonism & Related Disorders, 2012
- Lewy- and Alzheimer-type pathologies in Parkinson's disease dementia: which is more important?Brain, 2011
- CSF amyloid β 1-42 predicts cognitive decline in Parkinson diseaseNeurology, 2010
- Synergistic Interactions between Aβ, Tau, and α-Synuclein: Acceleration of Neuropathology and Cognitive DeclineJournal of Neuroscience, 2010
- Cerebrospinal tau, phospho‐tau, and beta‐amyloid and neuropsychological functions in Parkinson's diseaseMovement Disorders, 2009
- A clinico-pathological study of subtypes in Parkinson's diseaseBrain, 2009
- Parkinson Disease With DementiaAlzheimer Disease & Associated Disorders, 2009
- Aβ deposition is associated with enhanced cortical α-synuclein lesions in Lewy body diseasesNeurobiology of Aging, 2005